This revised application proposes an expanded program of clinical research and mentoring by Guila Glosser, Ph.D., an established clinical investigator, who is requesting support to enable her to 1) conduct a program of research focused on memory dysfunction in patients with temporal lobe epilepsy (TLE), 2) spend increased time mentoring junior clinical investigators, and 3) provide additional opportunities for clinical research for postdoctoral fellows. This award is intended to foster development of a model program that combines principles and methods from the "process" approach to clinical neuropsychology and "cognitive" approach to experimental neuropsychology in a unified manner for clinical assessment, treatment, research and training in neuropsychology. The proposed investigations will examine cognitive mechanisms underlying various symptoms of memory dysfunction in TLE patients. Studies will focus on TLE patients with the more severe, medically intractable, seizure disorders before and after they undergo anterior temporal lobectomy (ATL). Studies will address theoretical issues regarding the role of medial temporal lobe (MTL) structures in longterm memory, as well as clinical issues involving the use of pre-surgical functional neuroirnaging to predict memory change after ATL. Experimental hypotheses and test paradigms are based on theories and empirical results derived from investigations of MTL functions in rodents and nonhuman primates. Specific Aim 1: To test predictions from 2 competing theoretical accounts of the role of the MTL in memory. One account predicts that MTL lesions disrupt the capacity to form relational or configurational memory representations, while sparing memory for simple associations. The second account predicts that, owing to privileged connections between MTL structures and anatomically proximal neocortical regions, unilateral MTL lesions in humans impair memory processing for different types of contents (verbal versus nonverbal), irrespective of the kinds of associations involved in the new learning. Specific Aim 2: To test the hypothesis that an allocentric spatial memory deficit, such as the one documented following bilateral MTL lesions in nonhuman species, underlies memory dysfunction in humans with unilateral MTL lesions, and that this spatial deficit is specifically related to lesions of the MTL in the right or nonlanguage dominant hemisphere. Specific Aim 3: a) Using fMRI to demonstrate that allocentric spatial memory processing activates anterior MTL structures in healthy humans, while egocentric spatial memory processing activates posterior MTL and parietal regions. b) To assess the usefulness of presurgical fMRI activation measures during an allocentric spatial memory task for predicting memory performance following ATL.